Complement component 4 copy number variation and CYP21A2 genotype associations in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Complement component 4 copy number variation and CYP21A2 genotype associations in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
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DOI：
10.1007/s00439-012-1217-8
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发表时间：
2012-12
期刊：
影响因子：
5.3
通讯作者：
Merke, Deborah P.
中科院分区：
文献类型：
--
作者：
Chen, Wuyan;Xu, Zhi;Nishitani, Miki;Van Ryzin, Carol;McDonnell, Nazli B.;Merke, Deborah P.
21-羟化酶缺乏症（21-OHD）引起的先天性肾上腺皮质增生（CAH）是一种由CYP 21 A2突变引起的皮质醇生物合成的常染色体隐性遗传疾病。CYP 21 A2基因座存在基因拷贝数变异（CNV）增加。C4是编码补体成分4的邻近基因，其CNV与自身免疫性疾病易感性相关。对127例无关的21-OHD患者（100例经典型，27例非经典型）进行了RCCX（RP-C4-CYP 21-TNX）区域的综合遗传分析。C4拷贝数通过Southern印迹测定。评价C4 CNV和血清C4水平与CYP 21 A2突变和相关表型的关系。与CAH非经典型相关的最常见CYP 21 A2突变V281 L与高C4拷贝数相关（p=7.13×10−16）。大的CYP 21 A2缺失与低C4拷贝数相关（p=1.61×10−14）。与人群估计值相比，CAH患者中具有短C4基因的单调节性RCCX（自身免疫性疾病的危险因素）的发生率显著较低（2.8% vs. 10.6%; p=1.08×10−4）。CAH患者C4 CNV增加，突变特异性相关性可能对自身免疫性疾病具有保护作用。CYP 21 A2与邻近基因相关的研究提供了对CNV热点遗传学的深入了解，CNV热点是人类健康的重要决定因素。
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes complement component 4, is associated with autoimmune disease susceptibility. Comprehensive genetic analysis of the RCCX (RP-C4-CYP21-TNX) region was conducted in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. The most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p=7.13×10−16). Large CYP21A2 deletion was associated with low C4 copy number (p=1.61×10−14). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6%; p=1.08×10−4). CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.
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影响因子：
2
作者：
Chen, Wuyan;Kim, Mimi S.;Merke, Deborah P.
通讯作者：
Merke, Deborah P.
影响因子：
3.9
作者：
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影响因子：
5.3
作者：
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通讯作者：
LUTHMAN, H
影响因子：
5.8
作者：
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通讯作者：
Merke, Deborah P.
影响因子：
3.6
作者：
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通讯作者：
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